Story 1: Is The Ebola Dallas Strain (EDS), an airborne, contagious, incurable and lethal virus mutation, now the source of a world-wide pandemic? — The American People Demand To Be Told The Truth — Videos

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CDC: Airborne Ebola possible but unlikely

By Elise Viebeck

The Ebola virus becoming airborne is a possible but unlikely outcome in the current epidemic, Centers for Disease Control and Prevention (CDC) Director Tom Frieden said Tuesday.

The outbreak involves Ebola Zaire, a strain that is passed through bodily fluids, not the air. But some experts have expressed fear about viral mutations due to the unprecedented — and rising — number of Ebola cases.

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Frieden sought to allay those fears during a call with reporters.

“The rate of change [with Ebola] is slower than most viruses, and most viruses don’t change how they spread,” he said. Frieden is unofficially spearheading the U.S. response to Ebola.

“That is not to say it’s impossible that it could change [to become airborne],” he continued. “That would be the worst-case scenario. We would know that by looking at … what is happening in Africa. That is why we have scientists from the CDC on the ground tracking that.”

A change in the way Ebola spreads would make the virus significantly more dangerous. The disease kills roughly half the people it infects, and lacking a vaccine or cure, its traceable chain of transmission through bodily fluids is one reason officials believe they can contain it.

Still, there is almost no precedent for a human virus mutating to become transmissible in a different way, a key piece of evidence in weighing whether that kind of shift is likely for Ebola.

“We have so many problems with Ebola, let’s not make another one that, of course, is theoretically possible but is pretty way down on the list of likely issues,” infectious diseases expert William Schaffner of Vanderbilt University told Scientific American.

Frieden touted new progress against Ebola in West Africa and Dallas, where a Liberian man remains in critical condition, but warned that “globally, this is going to be a long, hard fight.”

The Dallas patient interacted with 10 definite and 38 possible interlocturos who are now being monitored, he said. None have shown symptoms.

Some Ebola experts worry virus may spread more easily than assumed

Ebola could be spread through air in tight quarters, some scientists fear
Some Ebola experts worry that the virus may spread more easily than thought — through the air in small spaces, for example.
By DAVID WILLMAN contact the reporter NationMedical ResearchAfricaScientific ResearchDiseases and IllnessesEbolaU.S. Centers for Disease Control and Prevention

Ebola researcher says he would not rule out possibility that the virus spreads through air in tight quarters
‘There are too many unknowns here,’ a virologist says of how Ebola may spread
Ebola researcher says he thinks there is a chance asymptomatic people could spread the virus
U.S. officials leading the fight against history’s worst outbreak of Ebola have said they know the ways the virus is spread and how to stop it. They say that unless an air traveler from disease-ravaged West Africa has a fever of at least 101.5 degrees or other symptoms, co-passengers are not at risk.

“At this point there is zero risk of transmission on the flight,” Dr. Thomas Frieden, director of the federal Centers for Disease Control and Prevention, said after a Liberian man who flew through airports in Brussels and Washington was diagnosed with the disease last week in Dallas.

First Ebola infection outside West Africa
Three more people have been hospitalized in Madrid for possible exposure to the Ebola virus after a Spanish nurse tested positive for the virus.
Other public health officials have voiced similar assurances, saying Ebola is spread only through physical contact with a symptomatic individual or their bodily fluids. “Ebola is not transmitted by the air. It is not an airborne infection,” said Dr. Edward Goodman of Texas Health Presbyterian Hospital in Dallas, where the Liberian patient remains in critical condition.

Yet some scientists who have long studied Ebola say such assurances are premature — and they are concerned about what is not known about the strain now on the loose. It is an Ebola outbreak like none seen before, jumping from the bush to urban areas, giving the virus more opportunities to evolve as it passes through multiple human hosts.

Dr. C.J. Peters, who battled a 1989 outbreak of the virus among research monkeys housed in Virginia and who later led the CDC’s most far-reaching study of Ebola’s transmissibility in humans, said he would not rule out the possibility that it spreads through the air in tight quarters.

“We just don’t have the data to exclude it,” said Peters, who continues to research viral diseases at the University of Texas in Galveston.

Dr. Philip K. Russell, a virologist who oversaw Ebola research while heading the U.S. Army’s Medical Research and Development Command, and who later led the government’s massive stockpiling of smallpox vaccine after the Sept. 11 terrorist attacks, also said much was still to be learned. “Being dogmatic is, I think, ill-advised, because there are too many unknowns here.”

If Ebola were to mutate on its path from human to human, said Russell and other scientists, its virulence might wane — or it might spread in ways not observed during past outbreaks, which were stopped after transmission among just two to three people, before the virus had a greater chance to evolve. The present outbreak in West Africa has killed approximately 3,400 people, and there is no medical cure for Ebola.

“I see the reasons to dampen down public fears,” Russell said. “But scientifically, we’re in the middle of the first experiment of multiple, serial passages of Ebola virus in man…. God knows what this virus is going to look like. I don’t.”
A resident looks from behind a gate during the Liberian government’s 11-day Ebola quarantine in the West Point district of Monrovia.
Tom Skinner, a spokesman for the CDC in Atlanta, said health officials were basing their response to Ebola on what has been learned from battling the virus since its discovery in central Africa in 1976. The CDC remains confident, he said, that Ebola is transmitted principally by direct physical contact with an ill person or their bodily fluids.

Skinner also said the CDC is conducting ongoing lab analyses to assess whether the present strain of Ebola is mutating in ways that would require the government to change its policies on responding to it. The results so far have not provided cause for concern, he said.

The researchers reached in recent days for this article cited grounds to question U.S. officials’ assumptions in three categories.

One issue is whether airport screenings of prospective travelers to the U.S. from West Africa can reliably detect those who might have Ebola. Frieden has said the CDC protocols used at West African airports can be relied on to prevent more infected passengers from coming to the U.S.

“One hundred percent of the individuals getting on planes are screened for fever before they get on the plane,” Frieden said Sept. 30. “And if they have a fever, they are pulled out of the line, assessed for Ebola, and don’t fly unless Ebola is ruled out.”

Individuals who have flown recently from one or more of the affected countries suggested that travelers could easily subvert the screening procedures — and might have incentive to do so: Compared with the depleted medical resources in the West African countries of Liberia, Sierra Leone and Guinea, the prospect of hospital care in the U.S. may offer an Ebola-exposed person the only chance to survive.

U.S. To Increase Airport Screening For Ebola
The deteriorating conditions in Africa make it more likely additional cases of Ebola will appear in the United States and officials are pushing for increased screenings at airports.
A person could pass body temperature checks performed at the airports by taking ibuprofen or any common analgesic. And prospective passengers have much to fear from identifying themselves as sick, said Kim Beer, a resident of Freetown, the capital of Sierra Leone, who is working to get medical supplies into the country to cope with Ebola.

“It is highly unlikely that someone would acknowledge having a fever, or simply feeling unwell,” Beer said via email. “Not only will they probably not get on the flight — they may even be taken to/required to go to a ‘holding facility’ where they would have to stay for days until it is confirmed that it is not caused by Ebola. That is just about the last place one would want to go.”

Liberian officials said last week that the patient hospitalized in Dallas, Thomas Eric Duncan, did not report to airport screeners that he had had previous contact with an Ebola-stricken woman. It is not known whether Duncan knew she suffered from Ebola; her family told neighbors it was malaria.
The potential disincentive for passengers to reveal their own symptoms was echoed by Sheka Forna, a dual citizen of Sierra Leone and Britain who manages a communications firm in Freetown. Forna said he considered it “very possible” that people with fever would medicate themselves to appear asymptomatic.

It would be perilous to admit even nonspecific symptoms at the airport, Forna said in a telephone interview. “You’d be confined to wards with people with full-blown disease.”

On Monday, the White House announced that a review was underway of existing airport procedures. Frieden and President Obama’s assistant for homeland security and counter-terrorism, Lisa Monaco, said Friday that closing the U.S. to passengers from the Ebola-affected countries would risk obstructing relief efforts.

CDC officials also say that asymptomatic patients cannot spread Ebola. This assumption is crucial for assessing how many people are at risk of getting the disease. Yet diagnosing a symptom can depend on subjective understandings of what constitutes a symptom, and some may not be easily recognizable. Is a person mildly fatigued because of short sleep the night before a flight — or because of the early onset of disease?
Moreover, said some public health specialists, there is no proof that a person infected — but who lacks symptoms — could not spread the virus to others.

“It’s really unclear,” said Michael Osterholm, a public health scientist at the University of Minnesota who recently served on the U.S. government’s National Science Advisory Board for Biosecurity. “None of us know.”

Russell, who oversaw the Army’s research on Ebola, said he found the epidemiological data unconvincing.
“The definition of ‘symptomatic’ is a little difficult to deal with,” he said. “It may be generally true that patients aren’t excreting very much virus until they become ill, but to say that we know the course of [the virus’ entry into the bloodstream] and the course of when a virus appears in the various secretions, I think, is premature.”

The CDC’s Skinner said that while officials remained confident that Ebola can be spread only by the overtly sick, the ongoing studies would assess whether mutations that might occur could increase the potential for asymptomatic patients to spread it.

Finally, some also question the official assertion that Ebola cannot be transmitted through the air. In late 1989, virus researcher Charles L. Bailey supervised the government’s response to an outbreak of Ebola among several dozen rhesus monkeys housed for research in Reston, Va., a suburb of Washington.

What Bailey learned from the episode informs his suspicion that the current strain of Ebola afflicting humans might be spread through tiny liquid droplets propelled into the air by coughing or sneezing.

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“We know for a fact that the virus occurs in sputum and no one has ever done a study [disproving that] coughing or sneezing is a viable means of transmitting,” he said. Unqualified assurances that Ebola is not spread through the air, Bailey said, are “misleading.”

Peters, whose CDC team studied cases from 27 households that emerged during a 1995 Ebola outbreak in Democratic Republic of Congo, said that while most could be attributed to contact with infected late-stage patients or their bodily fluids, “some” infections may have occurred via “aerosol transmission.”

Ailing in Monrovia, Liberia
Relatives pray over a weak Siata Johnson, 23, outside the Ebola treatment center at a hospital on the outskirts of Monrovia, Liberia. (John Moore / Getty Images)
Skinner of the CDC, who cited the Peters-led study as the most extensive of Ebola’s transmissibility, said that while the evidence “is really overwhelming” that people are most at risk when they touch either those who are sick or such a person’s vomit, blood or diarrhea, “we can never say never” about spread through close-range coughing or sneezing.

“I’m not going to sit here and say that if a person who is highly viremic … were to sneeze or cough right in the face of somebody who wasn’t protected, that we wouldn’t have a transmission,” Skinner said.

Peters, Russell and Bailey, who in 1989 was deputy commander for research of the Army’s Medical Research Institute of Infectious Diseases, in Frederick, Md., said the primates in Reston had appeared to spread Ebola to other monkeys through their breath.

The Ebola strain found in the monkeys did not infect their human handlers. Bailey, who now directs a biocontainment lab at George Mason University in Virginia, said he was seeking to research the genetic differences between the Ebola found in the Reston monkeys and the strain currently circulating in West Africa.

Though he acknowledged that the means of disease transmission among the animals would not guarantee the same result among humans, Bailey said the outcome may hold lessons for the present Ebola epidemic.

“Those monkeys were dying in a pattern that was certainly suggestive of coughing and sneezing — some sort of aerosol movement,” Bailey said. “They were dying and spreading it so quickly from cage to cage. We finally came to the conclusion that the best action was to euthanize them all.”

Dallas County Judge Clay Jenkins pulled into the Ivy Apartments community late in the evening Friday wearing suit pants and a lavender dress shirt.

There were hazardous materials trucks all around, as cleaning crews had arrived to remove materials that might have been touched by Thomas Duncan, a Liberian man who is hospitalized in Texas with Ebola. The hazmat workers were covered from head to toe in bright yellow body suits, green gloves and breathing masks.

Jenkins walked into the apartment in building No. 6 to greet Louise Troh, her family and others who live with her and had been court-ordered to stay in their home because they were considered high risk after coming into contact with Duncan.

It was time to move, and Troh, her 13-year old son, a relative of Duncan’s and another man — all of whom lived in the apartment — got into the judge’s car for the 45-minute drive to their new, temporary home, in an undisclosed part of Dallas.

Jenkins, the judge, never covered up.

“I’m a married man with a little girl,” Jenkins told reporters later that night. “I’m wearing the same shirt I was when I was in the car with that family.

“I was in their house next to those materials, meeting with them, listening to them, and assuring them last night and again of course today. If there were any risk, I would not expose myself or my family to that risk.”

He added: “There is zero risk.”

In the face of widespread fear — and in some cases misinformation — about Ebola following the first diagnosis of the virus in the United States, Dallas officials have taken a notable visual approach to make the point that, at least right now, the city is safe.
The Ebola outbreak in West Africa has reached the United States, as officials confirm one case in Dallas. Here’s how U.S. health officials plan to stop the virus. (Gillian Brockell and Jorge Ribas/The Washington Post)
On a daily basis, workers monitoring the temperatures and health of as many as nine individuals who they believe might have had direct contact with Duncan have entered those people’s homes with no gloves, no masks and no personal protective equipment whatsoever.

And city officials including Jenkins, Dallas Mayor Mike Rawlings and Dallas County Health and Human Services Director Zachary Thompson have interacted with the family no differently that they might have if the four people who are in a state of semi-isolation had been suspected of having come into contact with somebody sick with the flu.
“Based on our assessment, they were asymptomatic; therefore, I didn’t feel they posed any threat to me,” Thompson said in an interview with The Washington Post on Monday. “There is a standard procedure for when they should be using the PPE’s (personal protective equipment). In this case we knew our nurses, our staff, had assessed that they were asymptomatic.”

So far, none of the people who have potentially had contact with Duncan are showing any symptoms, Thompson said.

Yet concern and stigma are widespread in Dallas.

Photographs from Liberia, Sierra Leone and Guinea — where the epidemic is spiraling out of control — frequently show fully masked health workers carrying infected people to hospitals or burial sites. Those images have become closely associated with the virus and the outbreak in the public’s mind.

And for one day, similar images briefly appeared in Dallas as cleaning crews removed materials from Troh’s apartment that might have come into contact with the virus.
A hazmat team arrives on Oct. 3 to clean a unit at the Dallas apartment complex where the confirmed Ebola patient was staying. (Joe Raedle/Getty Images)
The decision for the crew to wear personal protective equipment was made by the company, the “Cleaning Guys,” according to Dallas officials.

“We train for this type of thing,” company executive Brad Smith told ABC News. “Obviously, we haven’t trained for Ebola because there hasn’t been a situation in Texas until now.”

The Ebola virus is not very hearty outside of the human body.

Still, touching and destroying potentially infected materials is far different from speaking to or being in the same room with people who might have been exposed to the virus.

And public health expert Gavin Macgregor-Skinner, who worked in Nigeria to end that country’s outbreak, said that treating people with a sense of humanity and not feeding hysteria is critical to managing the Dallas Ebola case and others that might occur around the world.

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“Even in West Africa when we do contact tracing, we don’t put on personal protective equipment,” said Macgregor-Skinner, an assistant professor in the Department of Public Health Sciences at the Penn State Milton S. Hershey Medical Center. “We have the six-feet rule: We stay about six feet away from people and I can interview them and I can make them feel like people.

“If they have no symptoms, we need to make them feel normal, like they’re part of the community, like they are still loved.”

Dallas officials have also urged residents to go about their normal activities and attend community gatherings and fairs without fear.

“The broader perspective is that we had done immediate disease tracking and contact tracing and the family had been identified who had had close contact and they had not shown any symptoms,” said Thompson. “Other than that one case, basically, his virus has been contained.”

‘In 1976 I discovered Ebola – now I fear an unimaginable tragedy’

Peter Piot was a researcher at a lab in Antwerp when a pilot brought him a blood sample from a Belgian nun who had fallen mysteriously ill in Zaire

Professor Peter Piot, the Director of the London School of Hygiene and Tropical Medicine: ‘Around June it became clear to me there was something different about this outbreak. I began to get really worried’ Photograph: Leon Neal/AFP

Professor Piot, as a young scientist in Antwerp, you were part of the team that discovered the Ebola virus in 1976. How did it happen?

I still remember exactly. One day in September, a pilot from Sabena Airlines brought us a shiny blue Thermos and a letter from a doctor in Kinshasa in what was then Zaire. In the Thermos, he wrote, there was a blood sample from a Belgian nun who had recently fallen ill from a mysterious sickness in Yambuku, a remote village in the northern part of the country. He asked us to test the sample for yellow fever.

These days, Ebola may only be researched in high-security laboratories. How did you protect yourself back then?

We had no idea how dangerous the virus was. And there were no high-security labs in Belgium. We just wore our white lab coats and protective gloves. When we opened the Thermos, the ice inside had largely melted and one of the vials had broken. Blood and glass shards were floating in the ice water. We fished the other, intact, test tube out of the slop and began examining the blood for pathogens, using the methods that were standard at the time.

But the yellow fever virus apparently had nothing to do with the nun’s illness.

No. And the tests for Lassa fever and typhoid were also negative. What, then, could it be? Our hopes were dependent on being able to isolate the virus from the sample. To do so, we injected it into mice and other lab animals. At first nothing happened for several days. We thought that perhaps the pathogen had been damaged from insufficient refrigeration in the Thermos. But then one animal after the next began to die. We began to realise that the sample contained something quite deadly.

But you continued?

Other samples from the nun, who had since died, arrived from Kinshasa. When we were just about able to begin examining the virus under an electron microscope, the World Health Organisation instructed us to send all of our samples to a high-security lab in England. But my boss at the time wanted to bring our work to conclusion no matter what. He grabbed a vial containing virus material to examine it, but his hand was shaking and he dropped it on a colleague’s foot. The vial shattered. My only thought was: “Oh, shit!” We immediately disinfected everything, and luckily our colleague was wearing thick leather shoes. Nothing happened to any of us.

In the end, you were finally able to create an image of the virus using the electron microscope.

Yes, and our first thought was: “What the hell is that?” The virus that we had spent so much time searching for was very big, very long and worm-like. It had no similarities with yellow fever. Rather, it looked like the extremely dangerous Marburg virus which, like ebola, causes a haemorrhagic fever. In the 1960s the virus killed several laboratory workers in Marburg, Germany.

Were you afraid at that point?

I knew almost nothing about the Marburg virus at the time. When I tell my students about it today, they think I must come from the stone age. But I actually had to go the library and look it up in an atlas of virology. It was the American Centres for Disease Control which determined a short time later that it wasn’t the Marburg virus, but a related, unknown virus. We had also learned in the meantime that hundreds of people had already succumbed to the virus in Yambuku and the area around it.

A few days later, you became one of the first scientists to fly to Zaire.

Yes. The nun who had died and her fellow sisters were all from Belgium. In Yambuku, which had been part of the Belgian Congo, they operated a small mission hospital. When the Belgian government decided to send someone, I volunteered immediately. I was 27 and felt a bit like my childhood hero, Tintin. And, I have to admit, I was intoxicated by the chance to track down something totally new.

A girl is led to an ambulance after showing signs of Ebola infection in the village of Freeman Reserve, 30 miles north of the Liberian capital, Monrovia. Photograph: Jerome Delay/APWas there any room for fear, or at least worry?

Of course it was clear to us that we were dealing with one of the deadliest infectious diseases the world had ever seen – and we had no idea that it was transmitted via bodily fluids! It could also have been mosquitoes. We wore protective suits and latex gloves and I even borrowed a pair of motorcycle goggles to cover my eyes. But in the jungle heat it was impossible to use the gas masks that we bought in Kinshasa. Even so, the Ebola patients I treated were probably just as shocked by my appearance as they were about their intense suffering. I took blood from around 10 of these patients. I was most worried about accidentally poking myself with the needle and infecting myself that way.

But you apparently managed to avoid becoming infected.

Well, at some point I did actually develop a high fever, a headache and diarrhoea …

… similar to Ebola symptoms?

Exactly. I immediately thought: “Damn, this is it!” But then I tried to keep my cool. I knew the symptoms I had could be from something completely different and harmless. And it really would have been stupid to spend two weeks in the horrible isolation tent that had been set up for us scientists for the worst case. So I just stayed alone in my room and waited. Of course, I didn’t get a wink of sleep, but luckily I began feeling better by the next day. It was just a gastrointestinal infection. Actually, that is the best thing that can happen in your life: you look death in the eye but survive. It changed my whole approach, my whole outlook on life at the time.

You were also the one who gave the virus its name. Why Ebola?

On that day our team sat together late into the night – we had also had a couple of drinks – discussing the question. We definitely didn’t want to name the new pathogen “Yambuku virus”, because that would have stigmatised the place forever. There was a map hanging on the wall and our American team leader suggested looking for the nearest river and giving the virus its name. It was the Ebola river. So by around three or four in the morning we had found a name. But the map was small and inexact. We only learned later that the nearest river was actually a different one. But Ebola is a nice name, isn’t it?

In the end, you discovered that the Belgian nuns had unwittingly spread the virus. How did that happen?

In their hospital they regularly gave pregnant women vitamin injections using unsterilised needles. By doing so, they infected many young women in Yambuku with the virus. We told the nuns about the terrible mistake they had made, but looking back I would say that we were much too careful in our choice of words. Clinics that failed to observe this and other rules of hygiene functioned as catalysts in all additional Ebola outbreaks. They drastically sped up the spread of the virus or made the spread possible in the first place. Even in the current Ebola outbreak in westAfrica, hospitals unfortunately played this ignominious role in the beginning.

After Yambuku, you spent the next 30 years of your professional life devoted to combating Aids. But now Ebola has caught up to you again. American scientists fear that hundreds of thousands of people could ultimately become infected. Was such an epidemic to be expected?

No, not at all. On the contrary, I always thought that Ebola, in comparison to Aids or malaria, didn’t present much of a problem because the outbreaks were always brief and local. Around June it became clear to me that there was something fundamentally different about this outbreak. At about the same time, the aid organisation Médecins Sans Frontières sounded the alarm. We Flemish tend to be rather unemotional, but it was at that point that I began to get really worried.

Why did WHO react so late?

On the one hand, it was because their African regional office isn’t staffed with the most capable people but with political appointees. And the headquarters in Geneva suffered large budget cuts that had been agreed to by member states. The department for haemorrhagic fever and the one responsible for the management of epidemic emergencies were hit hard. But since August WHO has regained a leadership role.

There is actually a well-established procedure for curtailing Ebola outbreaks: isolating those infected and closely monitoring those who had contact with them. How could a catastrophe such as the one we are now seeing even happen?

I think it is what people call a perfect storm: when every individual circumstance is a bit worse than normal and they then combine to create a disaster. And with this epidemic there were many factors that were disadvantageous from the very beginning. Some of the countries involved were just emerging from terrible civil wars, many of their doctors had fled and their healthcare systems had collapsed. In all of Liberia, for example, there were only 51 doctors in 2010, and many of them have since died of Ebola.

The fact that the outbreak began in the densely populated border region between Guinea, Sierra Leone and Liberia …

… also contributed to the catastrophe. Because the people there are extremely mobile, it was much more difficult than usual to track down those who had had contact with the infected people. Because the dead in this region are traditionally buried in the towns and villages they were born in, there were highly contagious Ebola corpses travelling back and forth across the borders in pickups and taxis. The result was that the epidemic kept flaring up in different places.

For the first time in its history, the virus also reached metropolises such as Monrovia and Freetown. Is that the worst thing that can happen?

In large cities – particularly in chaotic slums – it is virtually impossible to find those who had contact with patients, no matter how great the effort. That is why I am so worried about Nigeria as well. The country is home to mega-cities like Lagos and Port Harcourt, and if the Ebola virus lodges there and begins to spread, it would be an unimaginable catastrophe.

Have we completely lost control of the epidemic?

I have always been an optimist and I think that we now have no other choice than to try everything, really everything. It’s good that the United States and some other countries are finally beginning to help. But Germany or even Belgium, for example, must do a lot more. And it should be clear to all of us: This isn’t just an epidemic any more. This is a humanitarian catastrophe. We don’t just need care personnel, but also logistics experts, trucks, jeeps and foodstuffs. Such an epidemic can destabilise entire regions. I can only hope that we will be able to get it under control. I really never thought that it could get this bad.

What can really be done in a situation when anyone can become infected on the streets and, like in Monrovia, even the taxis are contaminated?

We urgently need to come up with new strategies. Currently, helpers are no longer able to care for all the patients in treatment centres. So caregivers need to teach family members who are providing care to patients how to protect themselves from infection to the extent possible. This on-site educational work is currently the greatest challenge. Sierra Leone experimented with a three-day curfew in an attempt to at least flatten out the infection curve a bit. At first I thought: “That is totally crazy.” But now I wonder, “why not?” At least, as long as these measures aren’t imposed with military power.

A three-day curfew sounds a bit desperate.

Yes, it is rather medieval. But what can you do? Even in 2014, we hardly have any way to combat this virus.

Do you think we might be facing the beginnings of a pandemic?

There will certainly be Ebola patients from Africa who come to us in the hopes of receiving treatment. And they might even infect a few people here who may then die. But an outbreak in Europe or North America would quickly be brought under control. I am more worried about the many people from India who work in trade or industry in west Africa. It would only take one of them to become infected, travel to India to visit relatives during the virus’s incubation period, and then, once he becomes sick, go to a public hospital there. Doctors and nurses in India, too, often don’t wear protective gloves. They would immediately become infected and spread the virus.

The virus is continually changing its genetic makeup. The more people who become infected, the greater the chance becomes that it will mutate …

… which might speed its spread. Yes, that really is the apocalyptic scenario. Humans are actually just an accidental host for the virus, and not a good one. From the perspective of a virus, it isn’t desirable for its host, within which the pathogen hopes to multiply, to die so quickly. It would be much better for the virus to allow us to stay alive longer.

Could the virus suddenly change itself such that it could be spread through the air?

Like measles, you mean? Luckily that is extremely unlikely. But a mutation that would allow Ebola patients to live a couple of weeks longer is certainly possible and would be advantageous for the virus. But that would allow Ebola patients to infect many, many more people than is currently the case.

But that is just speculation, isn’t it?

Certainly. But it is just one of many possible ways the virus could change to spread itself more easily. And it is clear that the virus is mutating.

You and two colleagues wrote a piece for the Wall Street Journalsupporting the testing of experimental drugs. Do you think that could be the solution?

Patients could probably be treated most quickly with blood serum from Ebola survivors, even if that would likely be extremely difficult given the chaotic local conditions. We need to find out now if these methods, or if experimental drugs like ZMapp, really help. But we should definitely not rely entirely on new treatments. For most people, they will come too late in this epidemic. But if they help, they should be made available for the next outbreak.

Testing of two vaccines is also beginning. It will take a while, of course, but could it be that only a vaccine can stop the epidemic?

I hope that’s not the case. But who knows? Maybe.

In Zaire during that first outbreak, a hospital with poor hygiene was responsible for spreading the illness. Today almost the same thing is happening. Was Louis Pasteur right when he said: “It is the microbes who will have the last word”?

Of course, we are a long way away from declaring victory over bacteria and viruses. HIV is still here; in London alone, five gay men become infected daily. An increasing number of bacteria are becoming resistant to antibiotics. And I can still see the Ebola patients in Yambuku, how they died in their shacks and we couldn’t do anything except let them die. In principle, it’s still the same today. That is very depressing. But it also provides me with a strong motivation to do something. I love life. That is why I am doing everything I can to convince the powerful in this world to finally send sufficient help to west Africa. Now!

The virus may be acquired upon contact with blood or bodily fluids of an infected human or other animal.[1] Spreading through the air has not been documented in the natural environment.[2]Fruit bats are believed to be a carrier and may spread the virus without being affected. Once human infection occurs, the disease may spread between people, as well. Male survivors may be able to transmit the disease via semen for nearly two months. To make the diagnosis, typically other diseases with similar symptoms such as malaria, cholera and other viral hemorrhagic fevers are first excluded. To confirm the diagnosis, blood samples are tested for viral antibodies, viralRNA, or the virus itself.[1]

Outbreak control require community engagement, case management, surveillance and contact tracing, a good laboratory service, and safe burials.[1] Prevention includes decreasing the spread of disease from infected animals to humans. This may be done by checking such animals for infection and killing and properly disposing of the bodies if the disease is discovered. Properly cooking meat and wearing protective clothing when handling meat may also be helpful, as are wearing protective clothing and washing hands when around a person with the disease. Samples of bodily fluids and tissues from people with the disease should be handled with special caution.[1]

Heavy bleeding is rare and is usually confined to the gastrointestinal tract.[12][15] In general, the development of bleeding symptoms often indicates a worse prognosis and this blood loss can result in death.[9] All people infected show some signs of circulatory system involvement, including impaired blood clotting.[12] If the infected person does not recover, death due to multiple organ dysfunction syndrome occurs within 7 to 16 days (usually between days 8 and 9) after first symptoms.[14]

Causes

EVD is caused by four of five viruses classified in the genus Ebolavirus, family Filoviridae, order Mononegavirales. The four disease-causing viruses are Bundibugyo virus (BDBV), Sudan virus (SUDV), Taï Forest virus (TAFV), and one called, simply, Ebola virus (EBOV, formerly Zaire Ebola virus)). Ebola virus is the sole member of the Zaire ebolavirus species and the most dangerous of the known Ebola disease-causing viruses, as well as being responsible for the largest number of outbreaks.[16] The fifth virus, Reston virus (RESTV), is not thought to be disease-causing in humans. These five viruses are closely related to the Marburg viruses.

Transmission

Human-to-human transmission can occur via direct contact with blood or bodily fluids from an infected person (including embalming of an infected dead person) or by contact with objects contaminated by the virus, particularly needles and syringes.[17] Other body fluids with ebola virus include saliva, mucus, vomit, feces, sweat, tears, breast milk, urine, and semen. Entry points include the nose, mouth, eyes, or open wounds, cuts and abrasions.[18] The potential for widespread EVD infections is considered low as the disease is only spread by direct contact with the secretions from someone who is showing signs of infection.[17] The symptoms limit a person’s ability to spread the disease as they are often too sick to travel.[19] Because dead bodies are still infectious, traditional burial rituals may spread the disease. Nearly two thirds of the cases of Ebola in Guinea during the 2014 outbreak are believed to be due to burial practices.[20][21] Semen may be infectious in survivors for up to 7 weeks.[1] It is not entirely clear how an outbreak is initially started.[22] The initial infection is believed to occur after ebola virus is transmitted to a human by contact with an infected animal’s body fluids.

One of the primary reasons for spread is that the health systems in the part of Africa where the disease occurs function poorly.[23] Medical workers who do not wear appropriate protective clothing may contract the disease.[24]Hospital-acquired transmission has occurred in African countries due to the reuse of needles and lack of universal precautions.[25][26] Some healthcare centers caring for people with the disease do not have running water.[27]

Airborne transmission has not been documented during EVD outbreaks.[2] They are, however, infectious as breathable 0.8– to 1.2-μm laboratory-generated droplets.[28] The virus has been shown to travel, without contact, from pigs to primates, although the same study failed to demonstrate similar transmission between non-human primates.[29]

Bats drop partially eaten fruits and pulp, then land mammals such as gorillas and duikers feed on these fallen fruits. This chain of events forms a possible indirect means of transmission from the natural host to animal populations, which has led to research towards viral shedding in the saliva of bats. Fruit production, animal behavior, and other factors vary at different times and places that may trigger outbreaks among animal populations.[30]

Reservoir

Bushmeat being prepared for cooking in Ghana, 2013. Human consumption of equatorial animals in Africa in the form of bushmeat has been linked to the transmission of diseases to people, including Ebola.[31]

Bats are considered the most likely natural reservoir of the EBOV. Plants, arthropods, and birds were also considered.[1][32] Bats were known to reside in the cotton factory in which the first cases for the 1976 and 1979 outbreaks were observed, and they have also been implicated in Marburg virus infections in 1975 and 1980.[33] Of 24 plant species and 19 vertebrate species experimentally inoculated with EBOV, only bats became infected.[34] The absence of clinical signs in these bats is characteristic of a reservoir species. In a 2002–2003 survey of 1,030 animals including 679 bats from Gabon and the Republic of the Congo, 13 fruit bats were found to contain EBOV RNA fragments.[35] As of 2005, three types of fruit bats (Hypsignathus monstrosus, Epomops franqueti, and Myonycteris torquata) have been identified as being in contact with EBOV. They are now suspected to represent the EBOV reservoir hosts.[36][37] Antibodies against Zaire and Reston viruses have been found in fruit bats in Bangladesh, thus identifying potential virus hosts and signs of the filoviruses in Asia.[38]

Between 1976 and 1998, in 30,000 mammals, birds, reptiles, amphibians and arthropods sampled from outbreak regions, no ebolavirus was detected apart from some genetic traces found in six rodents (Mus setulosus andPraomys) and one shrew (Sylvisorex ollula) collected from the Central African Republic.[33][39] Traces of EBOV were detected in the carcasses of gorillas and chimpanzees during outbreaks in 2001 and 2003, which later became the source of human infections. However, the high lethality from infection in these species makes them unlikely as a natural reservoir.[33]

Transmission between natural reservoir and humans is rare, and outbreaks are usually traceable to a single case where an individual has handled the carcass of gorilla, chimpanzee or duiker.[40] Fruit bats are also eaten by people in parts of West Africa where they are smoked, grilled or made into a spicy soup.[37][41]

Virology

Genome

Like all mononegaviruses, ebolavirions contain linear nonsegmented, single-strand, non-infectious RNAgenomes of negative polarity that possesses inverse-complementary 3′ and 5′ termini, do not possess a 5′ cap, are notpolyadenylated, and are not covalently linked to a protein.[42] Ebolavirus genomes are approximately 19 kilobase pairs long and contain seven genes in the order 3′-UTR–NP–VP35–VP40–GP–VP30–VP24–L–5′-UTR.[43] The genomes of the five different ebolaviruses (BDBV, EBOV, RESTV, SUDV, and TAFV) differ in sequence and the number and location of gene overlaps.

Structure

Like all filoviruses, ebolavirions are filamentous particles that may appear in the shape of a shepherd’s crook or in the shape of a “U” or a “6”, and they may be coiled, toroid, or branched.[43] In general, ebolavirions are 80 nm in width, but vary somewhat in length. In general, the median particle length of ebolaviruses ranges from 974 to 1,086 nm (in contrast to marburgvirions, whose median particle length was measured at 795–828 nm), but particles as long as 14,000 nm have been detected in tissue culture.[44]

Replication

The ebolavirus life cycle begins with virion attachment to specific cell-surface receptors, followed by fusion of the virion envelope with cellular membranes and the concomitant release of the virus nucleocapsid into the cytosol. The viral RNA polymerase, encoded by the L gene, partially uncoats the nucleocapsid and transcribes the genes into positive-strand mRNAs, which are then translated into structural and nonstructural proteins. Ebolavirus RNA polymerase (L) binds to a single promoter located at the 3′ end of the genome. Transcription either terminates after a gene or continues to the next gene downstream. This means that genes close to the 3′ end of the genome are transcribed in the greatest abundance, whereas those toward the 5′ end are least likely to be transcribed. The gene order is, therefore, a simple but effective form of transcriptional regulation. The most abundant protein produced is the nucleoprotein, whose concentration in the cell determines when L switches from gene transcription to genome replication. Replication results in full-length, positive-strand antigenomes that are, in turn, transcribed into negative-strand virus progeny genome copy. Newly synthesized structural proteins and genomes self-assemble and accumulate near the inside of the cell membrane. Virions bud off from the cell, gaining their envelopes from the cellular membrane they bud from. The mature progeny particles then infect other cells to repeat the cycle. The Ebola virus genetics are difficult to study due to its virulent nature.[45]

Pathophysiology

Pathogenesis schematic

Endothelial cells, macrophages, monocytes, and liver cells are the main targets of infection. After infection, a secreted glycoprotein (sGP) known as the Ebola virus glycoprotein (GP) is synthesized. Ebola replication overwhelms protein synthesis of infected cells and host immune defenses. The GP forms a trimeric complex, which binds the virus to the endothelial cells lining the interior surface of blood vessels. The sGP forms a dimeric protein that interferes with the signaling of neutrophils, a type of white blood cell, which allows the virus to evade the immune system by inhibiting early steps of neutrophil activation. These white blood cells also serve as carriers to transport the virus throughout the entire body to places such as the lymph nodes, liver, lungs, and spleen.[46]

The presence of viral particles and cell damage resulting from budding causes the release of chemical signals (to be specific, TNF-α, IL-6, IL-8, etc.), which are the signaling molecules for fever and inflammation. The cytopathic effect, from infection in the endothelial cells, results in a loss of vascular integrity. This loss in vascular integrity is furthered with synthesis of GP, which reduces specific integrins responsible for cell adhesion to the inter-cellular structure, and damage to the liver, which leads to improper clotting.[47]

Diagnosis

The travel and work history along with exposure to wildlife are important to consider when the diagnosis of EVD is suspected. The diagnosis is confirmed by isolating the virus, detecting its RNA or proteins, or detecting antibodiesagainst the virus in a person’s blood. Isolating the virus by cell culture, detecting the viral RNA by polymerase chain reaction (PCR) and detecting proteins by enzyme-linked immunosorbent assay (ELISA) works best early and in those who have died from the disease. Detecting antibodies against the virus works best late in the disease and in those who recover.[48]

During an outbreak, virus isolation is often not feasible. The most common diagnostic methods are therefore real-time PCR and ELISA detection of proteins, which can be performed in field or mobile hospitals.[49] Filovirions can be seen and identified in cell culture by electron microscopy due to their unique filamentous shapes, but electron microscopy cannot tell the difference between the various filoviruses despite there being some length differences.[44]

Classification

The genera Ebolavirus and Marburgvirus were originally classified as the species of the now-obsolete Filovirus genus. In March 1998, the Vertebrate Virus Subcommittee proposed in the International Committee on Taxonomy of Viruses (ICTV) to change the Filovirus genus to the Filoviridae family with two specific genera: Ebola-like viruses andMarburg-like viruses. This proposal was implemented in Washington, DC, on April 2001 and in Paris on July 2002. In 2000, another proposal was made in Washington, D.C., to change the “-like viruses” to “-virus” resulting in today’s Ebolavirus and Marburgvirus.[50]

Prevention

Infection control and containment

The risk of transmission is increased among those caring for people infected. Recommended measures when caring for those who are infected include isolating them, sterilizing equipment and surfaces, and wearing protective clothing including masks, gloves, gowns, and goggles.[22] If a person with Ebola dies, direct contact with the body of the deceased patient should be avoided.[22]

In order to reduce the spread, the World Health Organization recommends raising community awareness of the risk factors for Ebola infection and the protective measures individuals can take.[60] These include avoiding contact with infected people and regular hand washing using soap and water.[61] Traditional burial rituals, especially those requiring washing or embalming of bodies, should be discouraged or modified.[62][63] Social anthropologists may help find alternatives to traditional rules for burials.[64] Airline crews are instructed to isolate anyone who has symptoms resembling Ebola virus.[65]

The Ebola virus can be eliminated with heat (heating for 30 to 60 minutes at 60 °C or boiling for 5 minutes). On surfaces, some lipid solvents such as some alcohol-based products, detergents, sodium hypochlorite (bleach) or calcium hypochlorite (bleaching powder), and other suitable disinfectants at appropriate concentrations can be used as disinfectants.[66][67]

Quarantine

Quarantine, also known as enforced isolation, is usually effective in decreasing spread.[68][69] Governments often quarantine areas where the disease is occurring or individuals who may be infected.[70] In the United States, the law allows quarantine of those infected with Ebola.[71] During the 2014 outbreak, Liberia closed schools.[72]

Contact tracing

Contact tracing is regarded as important to contain an outbreak. It involves finding everyone who had close contact with infected individuals and watching for signs of illness for 21 days. If any of these contacts comes down with the disease, they should be isolated, tested, and treated. Then repeat the process by tracing the contacts’ contacts.[73][74]

Treatment

Standard support

A hospital isolation ward in Gulu, Uganda, during the October 2000 outbreak

Prognosis

The disease has a high mortality rate: often between 25 percent and 90 percent.[1][3] As of September 2014, information from WHO across all occurrences to date puts the overall fatality rate at 50%.[1] There are indications based on variations in death rate between countries that early and effective treatment of symptoms (e.g., supportive care to prevent dehydration) may reduce the fatality rate significantly.[78] If an infected person survives, recovery may be quick and complete. Prolonged cases are often complicated by the occurrence of long-term problems, such as inflammation of the testicles, joint pains, muscle pains, skin peeling, or hair loss. Eye symptoms, such as light sensitivity, excess tearing, iritis, iridocyclitis, choroiditis, and blindness have also been described. EBOV and SUDV may be able to persist in the semen of some survivors for up to seven weeks, which could give rise to infections and disease via sexual intercourse.[1]

1976

The first identified case of Ebola was on 26 August 1976, in Yambuku, a small rural village in Mongala District in northern Democratic Republic of the Congo (then known as Zaire).[79] The first victim, and the index case for the disease, was village school headmaster Mabalo Lokela, who had toured an area near the Central African Republic border along the Ebola river between 12–22 August. On 8 September he died of what would become known as the Ebola virus species of the ebolavirus.[80] Subsequently a number of other cases were reported, almost all centered on the Yambuku mission hospital or having close contact with another case.[80] 318 cases and 280 deaths (a 88% fatality rate) occurred in the DRC.[81] The Ebola outbreak was contained with the help of the World Health Organization and transport from the Congolese air force, by quarantining villagers, sterilizing medical equipment, and providing protective clothing. The virus responsible for the initial outbreak, first thought to be Marburg virus, was later identified as a new type of virus related to Marburg, and named after the nearby Ebola river. Another ebolavirus, the Sudan virus species, was also identified that same year when an outbreak occurred in Sudan, affecting 284 people and killing 151.[82]

1995 to 2013

The second major outbreak occurred in 1995 in the Democratic Republic of Congo, affecting 315 and killing 254. The next major outbreak occurred in Uganda in 2000, affecting 425 and killing 224; in this case the Sudan virus was found to be the ebolavirus species responsible for the outbreak.[83] In 2003 there was an outbreak in the Republic of Congo that affected 143 and killed 128, a death rate of 90%, the highest to date.[84]

In August 2007, 103 people were infected by a suspected hemorrhagic fever outbreak in the village of Kampungu, Democratic Republic of the Congo. The outbreak started after the funerals of two village chiefs, and 217 people in four villages fell ill.[83][85][86] The 2007 outbreak eventually affected 264 individuals and resulted in the deaths of 187.[1]

On 30 November 2007, the Uganda Ministry of Health confirmed an outbreak of Ebola in the Bundibugyo District in Western Uganda. After confirmation of samples tested by the United States National Reference Laboratories and the Centers for Disease Control, the World Health Organization confirmed the presence of a new species of Ebolavirus, which was tentatively named Bundibugyo.[87] The WHO reported 149 cases of this new strain and 37 of those led to deaths.[1]

The WHO confirmed two small outbreaks in Uganda in 2012. The first outbreak affected 7 people and resulted in the death of 4 and the second affected 24, resulting in the death of 17. The Sudan variant was responsible for both outbreaks.[1]

On 17 August 2012, the Ministry of Health of the Democratic Republic of the Congo reported an outbreak of the Ebola-Bundibugyo variant[88] in the eastern region.[89][90] Other than its discovery in 2007, this was the only time that this variant has been identified as the ebolavirus responsible for an outbreak. The WHO revealed that the virus had sickened 57 people and claimed 29 lives. The probable cause of the outbreak was tainted bush meat hunted by local villagers around the towns of Isiro and Viadana.[1][91]

2014 outbreak

In March 2014, the World Health Organization (WHO) reported a major Ebola outbreak in Guinea, a western African nation.[92] Researchers traced the outbreak to a two-year old child who died on 28 December 2013.[93][94] The disease then rapidly spread to the neighboring countries of Liberia and Sierra Leone. It is the largest Ebola outbreak ever documented, and the first recorded in the region.[92]

On 8 August 2014, the WHO declared the epidemic to be an international public health emergency. Urging the world to offer aid to the affected regions, the Director-General said, “Countries affected to date simply do not have the capacity to manage an outbreak of this size and complexity on their own. I urge the international community to provide this support on the most urgent basis possible.”[95] By mid-August 2014, Doctors Without Borders reported the situation in Liberia’s capital Monrovia as “catastrophic” and “deteriorating daily”. They reported that fears of Ebola among staff members and patients had shut down much of the city’s health system, leaving many people without treatment for other conditions.[96] By late August 2014, the disease had spread to Nigeria, and one case was reported in Senegal.[97][98][99][100] On 30 September 2014, the first confirmed case of Ebola was diagnosed in the United States at Texas Health Presbyterian Hospital in Dallas, Texas.[101]

Aside from the human cost, the outbreak has severely eroded the economies of the affected countries. A Financial Times report suggested the economic impact of the outbreak could kill more people than the virus itself. As of 23 September, in the three hardest hit countries, Liberia, Sierra Leone, and Guinea, there were only 893 treatment beds available while the current need was 2122. In a 26 September statement, the WHO said, “The Ebola epidemic ravaging parts of West Africa is the most severe acute public health emergency seen in modern times. Never before in recorded history has a biosafety level four pathogen infected so many people so quickly, over such a broad geographical area, for so long.”[102]

By 29 September 2014, 7,192 suspected cases and 3,286 deaths had been reported, however the World Health Organization has said that these numbers may be vastly underestimated.[103] The WHO reports that more than 216 healthcare workers are among the dead, partly due to the lack of equipment and long hours.[104][105]

History

The first recorded outbreak of EBD occurred in Southern Sudan in June 1976. A second outbreak soon followed in the Democratic Republic of the Congo (then Zaire).[106] Virus isolated from both outbreaks was named “Ebola virus” by Belgian researchers[107] after the Ebola River, located near the Zaire outbreak.[108] Although it was assumed that the two outbreaks were connected, scientists later realized that they were caused by distinct species of filoviruses, Sudan virus and Ebola virus.[106]

Shortly afterward, a US Army team headquartered at USAMRIID went into action to euthanize the monkeys which had not yet died, bringing those monkeys and those which had already died of the disease toFt. Detrick for study by the Army’s veterinary pathologists and virologists, and eventual disposal under safe conditions.[109]

Blood samples were taken from 178 animal handlers during the incident.[111] Of those, six animal handlers eventually seroconverted, including one who had cut himself with a bloody scalpel.[46][112] When the handlers did not become ill, the CDC concluded that the virus had a very low pathogenicity to humans.[112]

The Philippines and the United States had no previous cases of Ebola infection, and upon further isolation, researchers concluded it was another strain of Ebola, or a new filovirus of Asian origin, which they named Reston ebolavirus (REBOV) after the location of the incident.[109]

Other animals

Wild animals

It is widely believed that outbreaks of EVD among human populations result from handling infected wild animal carcasses. Some research suggests that an outbreak in the wild animals used for consumption, bushmeat, may result in a corresponding human outbreak. Since 2003, such outbreaks have been monitored through surveillance of animal populations with the aim of predicting and preventing Ebola outbreaks in humans.[119]

Recovered carcasses from gorillas contain multiple Ebola virus strains, which suggest multiple introductions of the virus. Bodies decompose quickly and carcasses are not infectious after three to four days. Contact between gorilla groups is rare, suggesting transmission among gorilla groups is unlikely, and that outbreaks result from transmission between viral reservoir and animal populations.[120]

Ebola has a high mortality among primates.[121] Frequent outbreaks of Ebola may have resulted in the deaths of 5,000 gorillas.[122] Outbreaks of Ebola may have been responsible for an 88% decline in tracking indices of observed chimpanzee populations in 420 square kilometer Lossi Sanctuary between 2002 and 2003.[120] Transmission among chimpanzees through meat consumption constitutes a significant risk factor, while contact between individuals, such as touching dead bodies and grooming, is not.[123]

Domesticated animals

Reston ebolavirus (REBOV) can be transmitted to pigs.[124] This virus was discovered during an outbreak of what at the time was thought to be simian hemorrhagic fever virus (SHFV) in crab-eating macaques in Reston, Virginia (hence the name Reston elabavirus) in 1989. Since the initial outbreak it has since been found in nonhuman primates in Pennsylvania, Texas, and Italy. In each case, the affected animals had been imported from a facility in the Philippines,[70] where the virus had infected pigs.[125] Despite its status as a Level‑4organism and its apparent pathogenicity in monkeys, REBOV has not caused disease in exposed human laboratory workers.[126] In 2012 it was demonstrated that the virus can travel without contact from pigs to nonhuman primates, although the same study failed to achieve transmission in that manner between primates.[124] According to the WHO, routine cleaning and disinfection of pig (or monkey) farms with sodium hypochlorite or other detergents should be effective in inactivating the Reston ebolavirus. If an outbreak is suspected, the area must be immediately quarantined.[82]

While pigs that have been infected with REBOV tend to show symptoms of the disease, it has been shown that dogs may become infected with EBOV and remain asymptomatic. Dogs in some parts of Africa scavenge for their food and it is known that they sometimes eat infected animals and the corpses of humans. Although they remain asymptomatic, a 2005 survey of dogs during an EBOV outbreak found that over 31.8% showed a seroprevalence for EBOV closest to an outbreak versus 9% a farther distance away.[127]

Research

A number of experimental treatments are being studied.[128] In the United States, the Food and Drug Administration (FDA)’s animal efficacy rule is being used to demonstrate reasonable safety to obtain permission to treat people who are infected with Ebola. It is being used as the normal path for testing drugs is not possible for diseases caused by dangerous pathogens or toxins. Experimental drugs are made available for use with the approval of regulatory agencies under named patient programs, known in the US as “expanded access”.[129] On 12 August 2014 the WHO released a statement that the use of not yet proven treatments is ethical in certain situations in an effort to treat or prevent the disease.[130]

Medications

Researchers looking at slides of cultures of cells that make monoclonal antibodies. These are grown in a lab and the researchers are analyzing the products to select the most promising of them.

As of August 14, 2014, the United States Food and Drug Administration (FDA) has not approved any drugs to treat or prevent Ebola and advises people to watch out for fraudulent products.[131] The unavailability of experimental treatments in the most affected regions during the 2014 outbreak spurred controversy, with some calling for experimental drugs to be made more widely available in Africa on a humanitarian basis, and others warning that making unproven experimental drugs widely available would be unethical, especially in light of past experimentation conducted in developing countries by Western drug companies.[132][133]

ZMapp is a monoclonal antibody vaccine. The limited supply of the drug has been used to treat a small number of individuals infected with the Ebola virus. Although some of these have recovered the outcome is not consideredstatistically significant.[138] ZMapp has proved effective in a trial involving Rhesus macaque monkeys.[139]

Antivirals

A number of antiviral medications are being studied. Favipiravir, an anti-viral drug approved in Japan for stockpiling against influenza pandemics, appears to be useful in a mouse model of Ebola.[9][140] On 4 October 2014, it was reported that a French nun who contracted Ebola while volunteering in Liberia was cured with Favipiravir treatment.[141]BCX4430 is a broad-spectrum antiviral drug developed by BioCryst Pharmaceuticals and currently being researched as a potential treatment for Ebola by USAMRIID.[142] The drug has been approved to progress to Phase 1 trials, expected late in 2014.[143]Brincidofovir, another broad-spectrum antiviral drug, has been granted an emergency FDA approval as an investigational new drug for the treatment of Ebola, after it was found to be effective against Ebolavirus in in vitro tests.[144] It has subsequently been used to treat the first patient diagnosed with Ebola in the USA, after he had recently returned from Liberia.[145] The antiviral drug lamivudine, which is usually used to treat HIV / AIDS, was reported in September 2014 to have been used successfully to treat 13 out of 15 Ebola-infected patients by a doctor in Liberia, as part of a combination therapy also involving intravenous fluids and antibiotics to combat opportunistic bacterial infection of Ebola-compromised internal organs.[146] Western virologists have however expressed caution about the results, due to the small number of patients treated and confounding factors present. Researchers at the NIH stated that lamivudine had so far failed to demonstrate anti-Ebola activity in preliminary in vitro tests, but that they would continue to test it under different conditions and would progress it to trials if even slight evidence for efficacy is found.[147]

A 2014 study found that three ion channel blockers used in the treatment of heart arrhythmias, amiodarone, dronedarone and verapamil, block the entry of Ebolavirus into cells in vitro.[153] Given their oral availability and history of human use, these drugs would be candidates for treating Ebola virus infection in remote geographical locations, either on their own or together with other antiviral drugs.

Melatonin has also been suggested as a potential treatment for Ebola based on promising in vitro results.[154]

Blood products

The WHO has stated that transfusion of whole blood or purified serum from Ebola survivors is the therapy with the greatest potential to be implemented immediately, although there is little information as to its efficacy.[155] At the end of September, WHO issued an interim guideline for this therapy.[156] The blood serum from those who have survived an infection is currently being studied to see if it is an effective treatment.[157] During a meeting arranged by WHO this research was deemed to be a top priority.[157] Seven of eight people with Ebola survived after receiving a transfusion of blood donated by individuals who had previously survived the infection in an 1999 outbreak in the Democratic Republic of the Congo.[76][158] This treatment, however, was started late in the disease meaning they may have already been recovering on their own and the rest of their care was better than usual.[76] Thus this potential treatment remains controversial.[77]Intravenous antibodies appear to be protective in non-human primates who have been exposed to large doses of Ebola.[159]The World Health Organisation has approved the use of convalescent serum and whole blood products to treat people with Ebola.[160]

Vaccines have protected nonhuman primates. Immunization takes six months, which impedes the counter-epidemic use of the vaccines. Searching for a quicker onset of effectiveness, in 2003, a vaccine using an adenoviral (ADV) vector carrying the Ebola spike protein was tested on crab-eating macaques. Twenty-eight days later, they were challenged with the virus and remained resistant.[162] A vaccine based on attenuated recombinant vesicular stomatitis virus (VSV) vector carrying either the Ebola glycoprotein or the Marburg glycoprotein in 2005 protected nonhuman primates,[171] opening clinical trials in humans.[167] The study by October completed the first human trial, over three months giving three vaccinations safely inducing an immune response. Individuals for a year were followed, and, in 2006, a study testing a faster-acting, single-shot vaccine began; this new study was completed in 2008.[168] Trying the vaccine on a strain of Ebola that more resembles one that infects humans is the next step.[172] On 6 December 2011, the development of a successfulvaccine against Ebola for mice was reported. Unlike the predecessors, it can be freeze-dried and thus stored for long periods in wait for an outbreak.[173] An experimental vaccine made by researchers at Canada’s national laboratory in Winnipeg was used, in 2009, to pre-emptively treat a German scientist who might have been infected during a lab accident.[174] However, actual EBOV infection was never demonstrated beyond doubt.[175] Experimentally, recombinant vesicular stomatitis Indiana virus (VSIV) expressing the glycoprotein of EBOV or SUDV has been used successfully in nonhuman primate models as post-exposure prophylaxis.[176][177] The CDC’s recommendations are currently under review.[citation needed]

Simultaneous phase 1 trials of an experimental vaccine known as the NIAID/GSK vaccine commenced in September 2014.[178]GlaxoSmithKline and the NIH jointly developed the vaccine,[178] based on a modified chimpanzee adenovirus, and contains parts of the Zaireand Sudan ebola strains.[178] If this phase is completed successfully, the vaccine will be fast tracked for use in West Africa. In preparation for this, GSK is preparing a stockpile of 10,000 doses.[179][180]